Smudge Cells in Chronic Lymphocytic Leukemia: Pathophysiology, Laboratory Considerations, and Clinical Significance

Marionneaux, Steven; Keohane, Elaine M.; Lamanna, Nicole; King, Thomas C.; Mehta, Shashi

doi:10.1093/labmed/lmaa119

Cited by 6 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The International Council for Standardization in Hematology (ICSH) recommends a solution for preparing and classifying smudge cells in peripheral blood after processing with one part of albumin and four parts of peripheral blood ( 25 ). Adding BSA to ethylenediaminetetraacetic acid (EDTA) acid-anticoagulated blood specimens for blood smears reduces the number of smudge cells and improves the consistency of morphological evaluation of peripheral blood smears in patients with chronic lymphocytic leukemia (CLL) patients ( 26 , 27 ). In a routine blood sample from a patient with CLL, 82 smudge cells were observed when 100 white blood cells were counted using CellaVision DI-60 software ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio

Wang,

Qin,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundNeutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge.ObjectiveWe employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19.MethodsPeripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators.ResultsMorphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels.ConclusionObserving blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.

show abstract

Section: Resultsmentioning

confidence: 99%

An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio

Wang,

Qin,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…More precise estimates of tumor burden would include absolute lymphocyte count (ALC) and number of B lymphocytes. Both ALC and WBC counts can suffer from inaccuracies due to the prevalence of smudge cells in CLL, often resulting in an underestimate of these counts [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Inferring parameters of cancer evolution in chronic lymphocytic leukemia

Lee

Božić

2022

PLoS Comput Biol

View full text Add to dashboard Cite

As a cancer develops, its cells accrue new mutations, resulting in a heterogeneous, complex genomic profile. We make use of this heterogeneity to derive simple, analytic estimates of parameters driving carcinogenesis and reconstruct the timeline of selective events following initiation of an individual cancer, where two longitudinal samples are available for sequencing. Using stochastic computer simulations of cancer growth, we show that we can accurately estimate mutation rate, time before and after a driver event occurred, and growth rates of both initiated cancer cells and subsequently appearing subclones. We demonstrate that in order to obtain accurate estimates of mutation rate and timing of events, observed mutation counts should be corrected to account for clonal mutations that occurred after the founding of the tumor, as well as sequencing coverage. Chronic lymphocytic leukemia (CLL), which often does not require treatment for years after diagnosis, presents an optimal system to study the untreated, natural evolution of cancer cell populations. When we apply our methodology to reconstruct the individual evolutionary histories of CLL patients, we find that the parental leukemic clone typically appears within the first fifteen years of life.

show abstract

“…It contains cellular entities that have lost their structural integrity and cannot be morphologically classified any further. Classically, on the peripheral blood smear, the smudge cells have been thought to represent degenerated lymphocytes (DL), which are abundant in blood smears of patients with chronic lymphocytic leukemia (CLL) [ 22 ]. Such smudge cells are a result of breakdown of fragile leukemic lymphocytes and, therefore, represent an artifact of smear preparation [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Classically, on the peripheral blood smear, the smudge cells have been thought to represent degenerated lymphocytes (DL), which are abundant in blood smears of patients with chronic lymphocytic leukemia (CLL) [ 22 ]. Such smudge cells are a result of breakdown of fragile leukemic lymphocytes and, therefore, represent an artifact of smear preparation [ 22 ]. We observed that a proportion of cell derived entities categorized as smudge cells by CellaVision ® morphologically resembled NETs.…”

Section: Introductionmentioning

confidence: 99%

Identifying Neutrophil Extracellular Traps (NETs) in Blood Samples Using Peripheral Smear Autoanalyzers

Fedorov

Barouqa

Yin

et al. 2023

Life

View full text Add to dashboard Cite

Neutrophil Extracellular Traps (NETs) are large neutrophil-derived structures composed of decondensed chromatin, cytosolic, and granule proteins. NETs play an important role in fighting infection, inflammation, thrombosis, and tumor progression processes, yet their fast and reliable identification has been challenging. Smudge cells (SCs) are a subcategory of white cells identified by CellaVision®, a hematology autoanalyzer routinely used in clinical practice that uses digital imaging to generate “manual” differentials of peripheral blood smears. We hypothesize that a proportion of cells identified in the SC category by CellaVision® Hematology Autoanalyzers are actually NETs. We demonstrate that NET-like SCs are not present in normal blood samples, nor are they an artifact of smear preparation. NET-like SCs stain positive for neutrophil markers such as myeloperoxidase, leukocyte alkaline phosphatase, and neutrophil elastase. On flow cytometry, cells from samples with high percent NET-like SCs that are positive for surface DNA are also positive for CD45, myeloperoxidase and markers of neutrophil activation and CD66b. Samples with NET-like SCs have a strong side fluorescent (SFL) signal on the white count and nucleated red cells (WNR) scattergram, representing cells with high nucleic acid content. When compared to patients with low percent SCs, those with a high percentage of SCs have a significantly higher incidence of documented bacterial and viral infections. The current methodology of NET identification is time-consuming, complicated, and cumbersome. In this study, we present data supporting identification of NETs by CellaVision®, allowing for easy, fast, cost-effective, and high throughput identification of NETs that is available in real time and may serve as a positive marker for a bacterial or viral infections.

show abstract

Smudge Cells in Chronic Lymphocytic Leukemia: Pathophysiology, Laboratory Considerations, and Clinical Significance

Cited by 6 publications

References 49 publications

An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio

An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio

Inferring parameters of cancer evolution in chronic lymphocytic leukemia

Identifying Neutrophil Extracellular Traps (NETs) in Blood Samples Using Peripheral Smear Autoanalyzers

Contact Info

Product

Resources

About